Interleukin 6 IL6

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IL-6 plays a key role in immune response regulation, acute phase response, and autoimmune activation.

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Interleukin 6 (IL-6) Test Information Guide

Why is it done?
- Test Measurement: IL-6 is a cytokine (signaling protein) produced primarily by immune cells, fibroblasts, and endothelial cells. This test measures the blood level of IL-6, a key marker of systemic inflammation and immune response.
- Primary Indications: Assessing systemic inflammation, monitoring autoimmune diseases, evaluating sepsis and severe infections, assessing cardiovascular risk, monitoring cancer progression, evaluating inflammatory bowel disease, and detecting cytokine storm in severe COVID-19
- Clinical Circumstances: Performed during acute illness, chronic disease monitoring, post-operative assessment, evaluation of fever of unknown origin, assessment of graft rejection, monitoring treatment response in inflammatory conditions, and in critical care settings for risk stratification
Normal Range
- Reference Range: <7.0 pg/mL (picograms per milliliter) for healthy adults. Some laboratories report values <5.0 or <10.0 pg/mL depending on their assay methodology.
- Units of Measurement: pg/mL (picograms per milliliter) or pmol/L (picomoles per liter). The reference range may vary between laboratories based on their specific assay platform and calibration.
- Result Interpretation: Normal: <7.0 pg/mL indicates minimal systemic inflammation.
- Elevated (>7.0 pg/mL): Indicates increased systemic inflammation, immune activation, or acute phase response. The degree of elevation correlates with inflammation severity.
- Borderline Values (5-10 pg/mL): Warrant repeat testing and clinical correlation to confirm significance.
- Critical Values: >100 pg/mL typically indicates severe inflammation, sepsis, or significant immune dysregulation requiring immediate clinical attention.
Interpretation
- Mildly Elevated (7-20 pg/mL): Suggests subclinical or mild systemic inflammation. May be seen in early infection, mild autoimmune activity, or chronic low-grade inflammation.
- Moderately Elevated (20-100 pg/mL): Indicates significant systemic inflammation consistent with acute infection, active rheumatoid arthritis, inflammatory bowel disease flare, or post-operative inflammation.
- Markedly Elevated (>100 pg/mL): Suggests severe inflammation, sepsis, severe COVID-19 with cytokine storm, acute leukemia, lymphoma, or major trauma with systemic inflammatory response.
- Factors Affecting Results:
- Time of day (circadian variation), recent exercise or physical stress, acute emotional stress, recent vaccinations, medication use (corticosteroids decrease IL-6), age (tends to increase with age), obesity (associated with higher baseline IL-6), smoking status, menstrual cycle phase in women
- Clinical Significance of Patterns:
- Rising IL-6: Suggests worsening inflammation or new-onset infection; serial measurements more informative than single values. Persistently elevated IL-6 in critical illness predicts poor prognosis. In autoimmune diseases, elevated IL-6 correlates with disease activity.
- Declining IL-6: Suggests treatment response or resolution of acute inflammation. Rapid drop may indicate effective immune modulation or removal of inflammatory source.
Associated Organs
- Primary Organ Systems: Immune system (T cells, B cells, macrophages), vascular endothelium, liver (hepatocyte production), musculoskeletal system (fibroblasts), central nervous system, and bone marrow.
- Associated Conditions with Elevated IL-6:
- Autoimmune Diseases: Rheumatoid arthritis, systemic lupus erythematosus, vasculitis, ankylosing spondylitis, Behçet's disease
- Infections: Bacterial sepsis, viral infections (COVID-19, influenza, EBV), fungal infections, tuberculosis, meningitis, pneumonia
- Inflammatory Bowel Diseases: Crohn's disease, ulcerative colitis (elevated during flares)
- Cardiovascular Conditions: Acute coronary syndrome, myocardial infarction, atherosclerosis, heart failure, coronary artery disease
- Malignancies: Lymphoma, leukemia, colorectal cancer, breast cancer, lung cancer (IL-6 promotes tumor progression)
- Metabolic Disorders: Type 2 diabetes, obesity, metabolic syndrome
- Other Conditions: Post-operative inflammation, trauma, burns, aging-related inflammation (inflammaging), depression and mood disorders
- Potential Complications from Elevated IL-6: Systemic inflammatory response syndrome (SIRS), multi-organ dysfunction, thrombotic events (IL-6 promotes coagulation), vascular permeability leading to shock, accelerated atherosclerosis, increased cardiovascular mortality risk, cytokine storm (life-threatening), organ damage, and disease progression.
Follow-up Tests
- Complementary Inflammatory Markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β)
- Complete Blood Count (CBC): To assess for infection (elevated WBC), anemia, or hematologic malignancy.
- Comprehensive Metabolic Panel (CMP): To assess organ function (hepatic, renal) and electrolytes, as severe inflammation may affect multiple organ systems.
- Coagulation Studies (PT/INR, aPTT): IL-6 promotes coagulation; assess for disseminated intravascular coagulation (DIC) in severe inflammation.
- Lactate Level: Elevated in sepsis and tissue hypoxia accompanying severe inflammation.
- Autoimmune Panel (if indicated): ANA, rheumatoid factor, anti-CCP, complement levels (C3, C4), ESR to evaluate for autoimmune disease.
- Blood Cultures: If infection suspected to identify causative organism.
- Imaging Studies: Chest X-ray, CT imaging, ultrasound to identify source of inflammation (pneumonia, abscess, malignancy).
- Disease-Specific Tests: Fecal calprotectin (IBD), TNF blocker levels, TSH (thyroid), cardiac troponin (ACS).
- Serial IL-6 Measurements: Repeat testing at 24-48 hour intervals in acute settings to track inflammation trends. Single values less informative than serial measurements showing trends.
- Monitoring Frequency: Acute illness: Every 24-48 hours; Chronic disease: Baseline and every 3-6 months; Autoimmune disease on treatment: Every 6-12 weeks; Post-operative: Daily until discharge; Critical care: Every 12-24 hours.
Fasting Required?
- Fasting Requirement: NO - Fasting is not required for IL-6 testing.
- Sample Collection Timing: Blood can be drawn at any time of day. However, note that IL-6 shows circadian variation (typically higher in early morning), so consistent timing is preferred for serial measurements.
- Patient Preparation Instructions:
- No special fasting requirements • Continue all regular medications as prescribed • Avoid strenuous exercise for 24 hours before testing (can elevate IL-6) • Avoid extreme stress if possible • Stay well-hydrated • Arrive well-rested for testing • Wear comfortable, loose-fitting clothing to facilitate blood draw
- Medications - No Need to Avoid: Take all regularly prescribed medications including blood pressure medications, diabetes medications, and cardiac medications. NSAIDs, antibiotics, and corticosteroids may affect IL-6 levels but should be continued as prescribed.
- Important Considerations: Report fever, current infection symptoms, recent vaccinations, or recent surgery to phlebotomist • Inform technician of recent strenuous exercise or emotional stress • For accurate serial comparisons, attempt to draw blood at same time of day • Sample should be processed within 2 hours of collection • Inform provider of all current medications and supplements

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